Venous catheters play critical roles in the administration of chemotherapy, antibiotics, blood, blood products and total parenteral nutrition essential for the successful treatment of many chronic afflictions. Recent advances in catheter technology have enabled the explosive growth in oncology (vascular access ports), nephrology (hemodialysis catheters) and inpatient interventions (peripherally inserted catheters). Unfortunately, the catheter surface interaction with the blood stream has a very high potential of initiating surface thrombi that lead to serious and often life-threatening complications. To counter this risk, patients are given systemic anticoagulation drugs, which, while reducing the probability of surface clotting, introduce a second set of serious medical complications that significantly increase patient morbidity and mortality. Current treatments to prevent catheter-related thrombosis rely primarily on IV/oral anticoagulation. However, the tradeoff between long-term IV/oral anticoagulation and internal bleeding severely limits the performance of these powerful devices. Many approaches have been studied to reduce the formation of surface clots associated with the use of venous catheters, but none have met with more than minimal success. However, we have recently discovered an approach to modifying one of the most commonly used catheter biomaterials in such a manner as to drastically reduce the formation of surface clots during the long periods that such catheters must remain within the body. This modification appears to have not only the potential to be medically effective, but also to allow the fabrication of improved venous catheters with minimal or no increase in cost. In Phase I of this project, we shall compound the new plastic and conduct in-vitro tests to demonstrate that the compound (a) can be readily made, (b) that its mechanical properties are similar to those biomaterials now most commonly used for making catheters, and (c) that it has dramatically reduced tendencies to instigate the formation of surface clots in appropriate baths of platelet rich media. In Phase II, the formulation of the optimal composition of the biomaterial will be completed and actual venous catheters will be made and used for extensive in-vitro tests as well as for testing in animals. By the completion of the project, the groundwork should have been set for final engineering and rapid commercialization of anti-thrombotic venous catheters which should lead directly to substantially improved patient outcome. PUBLIC HEALTH RELEVANCE Long-term, implantable, venous catheters have a very high potential of initiating surface thrombi that lead to serious and often life-threatening complications for a wide variety of patients. The proposed research will develop and evaluate a unique catheter biomaterial that addresses the two primary mechanisms of thrombus initiation, platelet adhesion and fibrinogen adsorption. The availability of such a biomaterial will enable the low cost production of anti-thrombotic catheters to improve the outcome of the large number of patients for whom implantable catheters are a critical part of their treatment. [unreadable] [unreadable] [unreadable]